TAKING AIM AT NON-ALCOHOLIC FATTY LIVER DISEASE

Texas A&M University System researchers in collaboration with the Department
of Veterans Affairs and Baylor Scott & White Research Institute have
completed a study identifying one of the mechanisms leading to the development
of non-alcoholic fatty liver disease, or NAFLD, providing new possibilities
for prevention and treatment of the disease.

The study, which included input from researchers affiliated with Wuhan
University, Huazhong University of Science and Technology, Chongqing Medical
University, Peking University, Augusta University and the Central Texas
Veterans Health Care System was published in the journal
Hepatology. It can currently be found online at
http://onlinelibrary.wiley.com/doi/10.1002/hep.29777/abstract.

Dr. Chaodong Wu. (Texas A&M AgriLife Research photo)

"Our research involved the adenosine 2A receptor, which plays a protective
role against tissue damage," said Dr. Chaodong Wu, a Texas A&M
AgriLife Research scientist in the nutrition and food science department
of Texas A&M University in College Station. "It can reduce overactive
immune cell activity, protecting tissues from being damaged by inflammation.
However, until now its role in protecting from tissue damage relative
to non-alcoholic fatty liver disease was largely unknown."

Wu said through this study, the researchers examined the effects disrupting
this receptor would have on aspects of obesity-associated NAFLD so they
could understand the underlying mechanisms.

"While these receptors normally serve as a protective mechanism, they
may be destructive if they become disrupted," he said. "For
our study we used receptor-disrupted animal models for comparison to a
control."

Both animal model groups were fed a high-fat diet to induce NAFLD, then
were examined for inflammatory and metabolic responses.

Dr. Gianfranco Alpini. (Photo courtesy Texas A&M College of Medicine)

"The results showed those models with the disrupted receptor had an
increased severity of fatty liver disease and inflammation compared to
the control model fed the same high-fat diet," said Dr. Gianfranco
Alpini, distinguished professor in the medical physiology department at
Texas A&M College of Medicine. Alpini is also a senior research scientist
at Central Texas Veterans Health Care System and director of the Baylor
Scott & White Digestive Disease Research Center.

"Receptor deficiency also significantly increased the amount of a
regulatory element-binding protein in the liver cells of fasted animal
models," said Dr. Heather Francis, associate professor of medical
physiology at Texas A&M College of Medicine and the study's co-author.
"The increase in this protein was commensurate with an associated
increase in the potential for fatty deposits in the liver."

Wu said the accumulative study results demonstrated receptor disruption
in both macrophages and liver cells accounts for increased severity of
NAFLD, likely through increasing inflammation and elevating fat deposits
by stimulating the activity of a factor controlling protein expression
of fat deposition.

"Overall, the study validates the importance of adenosine 2A receptor
as a therapeutic and/or preventive target for NAFLD," Wu said. "This
is significant in that it demonstrates the feasibility of targeting that
receptor to treat non-alcoholic fatty liver disease by means of its activation."

He said based on the results generated, once bioactive food components
capable of activating the receptor can be identified, these components
and foods enriched with these components can be used to help prevent non-alcoholic
fatty liver disease.

Wu said the study would not have been possible without the collaboration
of the Central Texas Veterans Health Care System and Baylor Scott &
White Research Institute's team at the Baylor Scott & White Digestive
Disease Research Center.

"Many members of the study team, including Alpini and Francis, as
well as Drs. Fanyin Meng and Shannon Glaser, associate professor of medical
physiology at Texas A&M College of Medicine, are also affiliated with
one or more of these institutions," he said.